Journal of Molecular Cell Biology最新文献_第5页

Structural basis of complex assembly and nucleosome recognition by the chromatin remodeling ncBAF complex. 染色质重塑ncBAF复合体的复合体组装和核小体识别的结构基础。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-30 DOI: 10.1093/jmcb/mjag020

Wancheng Xu, Shengsheng Ma, Yi Li, Muchun Li, Chihang Li, Yue Yin, Qingrun Li, Jingdong Cheng, Yong Chen

{"title":"Structural basis of complex assembly and nucleosome recognition by the chromatin remodeling ncBAF complex.","authors":"Wancheng Xu, Shengsheng Ma, Yi Li, Muchun Li, Chihang Li, Yue Yin, Qingrun Li, Jingdong Cheng, Yong Chen","doi":"10.1093/jmcb/mjag020","DOIUrl":"https://doi.org/10.1093/jmcb/mjag020","url":null,"abstract":"BRG1/BRM-associated factor (BAF)-family chromatin remodelers regulate transcription and genome organization by repositioning nucleosomes. The human non-canonical BAF (ncBAF) complex is uniquely defined by the presence of BRD9 and GLTSCR1/GLTSCR1L, as well as the absence of the ARID1/2 scaffold and the canonical nucleosome-binding module found in cBAF and PBAF. How ncBAF assembles and engages nucleosomes remains elusive. Here, we present a cryo-EM structure of ncBAF bound to a nucleosome, integrated with biochemical assays and crosslinking mass spectrometry analyses. The ncBAF complex adopts a three-module architecture comprising an ATPase motor module, a repositioned actin-related protein (ARP) module, and a highly flexible Base module. The ncBAF-specific subunits BRD9 and GLTSCR1L are largely dispensable for complex assembly and nucleosome remodeling. Instead, BCL7A directly engages the H2A-H2B acidic patch and the H2A N-terminal tail, providing a structural substitute for SMARCB1 in stimulating remodeling activity. These findings reveal how ncBAF compensates for the loss of the canonical nucleosome-binding module through modular reorganization, providing a structural framework for understanding ncBAF-mediated chromatin regulation and its roles in development and disease.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microtubule-associated CCDC112 is essential for spermiogenesis and male fertility in mice. 微管相关的CCDC112对小鼠精子发生和雄性生育能力至关重要。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-25 DOI: 10.1093/jmcb/mjag019

Qingchao Li, Xirui Zi, Yue Lu, Hanxiao Yin, Qian Lyu, Junhao Han, Huixin Shen, Xiaoqian Meng, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song

{"title":"Microtubule-associated CCDC112 is essential for spermiogenesis and male fertility in mice.","authors":"Qingchao Li, Xirui Zi, Yue Lu, Hanxiao Yin, Qian Lyu, Junhao Han, Huixin Shen, Xiaoqian Meng, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song","doi":"10.1093/jmcb/mjag019","DOIUrl":"https://doi.org/10.1093/jmcb/mjag019","url":null,"abstract":"Defective sperm motility is frequently associated with male infertility. The immotile short-tail sperm (ISTS) defect is a rare condition in which most sperm cells have abnormally short tails, impairing their motility and leading to infertility. Despite its implications, the genetic factors related to the ISTS defect remain largely unclear. In this study, we identify coiled-coil domain-containing 112 (CCDC112) as a critical factor for sperm tail formation. CCDC112 can associate with microtubules and interact with multiple centrosomal proteins, including PCM1, TEX9, and taxilin. Disruption of CCDC112 expression profoundly affects the cellular distribution of PCM1. Interestingly, the knockout of Ccdc112 in mice impacts spermiogenesis, resulting in the ISTS defect and ultimately causing male infertility. Furthermore, quantitative proteomic analysis highlights the essential role of CCDC112 in regulating axonemal microtubule inner proteins. We thus characterize CCDC112 as a microtubule-associated protein and substantiate its genetic link to ISTS-related male infertility.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumorigenic p53N236S balances aging and tumorigenesis via regulating DREAM/MMB and downstream telomere DNA replication pathways. 致瘤性p53N236S通过调节DREAM/MMB和下游端粒DNA复制途径平衡衰老和肿瘤发生。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-17 DOI: 10.1093/jmcb/mjaf053

Qianqian Wang, Haili Li, Quan Zheng, Jun Yang, Kailong Hou, Liangxia Jiang, Shuting Jia, Xiaoming Wu, Juhua Dan, Ying Luo

{"title":"Tumorigenic p53N236S balances aging and tumorigenesis via regulating DREAM/MMB and downstream telomere DNA replication pathways.","authors":"Qianqian Wang, Haili Li, Quan Zheng, Jun Yang, Kailong Hou, Liangxia Jiang, Shuting Jia, Xiaoming Wu, Juhua Dan, Ying Luo","doi":"10.1093/jmcb/mjaf053","DOIUrl":"10.1093/jmcb/mjaf053","url":null,"abstract":"The Werner syndrome (WS) is characterized with both premature aging and tumorigenic phenotypes. In this study, we introduced a tumorigenic mutation p53N236S (referred to as p53S later), which is found in immortalized WS mouse embryo fibroblasts, back into WS mice to investigate its impact on the telomere dysfunction-induced aging process. Intriguingly, the introduction of p53S rescued the aging phenotypes of WS mice, showing the extension of the lifespan and the delay in organ degeneration. Further studies revealed that the introduction of p53S transcriptionally upregulated the DREAM/MMB pathway and downstream DNA helicases and telomere maintenance proteins, facilitated the recruitment of these proteins to G-quadruplex (G4) DNA structures proximal to DNA replication forks, and promoted the unwinding of G4. By comparing the cellular responses to pyridostatin and hydroxyurea, respectively, we confirmed that p53S specifically regulates G4-related DNA replication stress. Thus, p53S compensates the loss of Wrn and telomerase function, solves the DNA replication, telomere lengthening, and cell proliferation problems in WS cells, and ultimately rescues the aging phenotypes of WS. Together, our data indicate that certain tumorigenic features can be applied to balance with premature aging, rescuing the aging phenotype without tumorigenic risk. This study suggests a new mechanism in aging regulation and provides the possibility of developing a tumor-free longevity strategy and targeting G4 and DNA replication in aging-related tumor therapy.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging role of FUS in TGFB1 and COL1A1 transcription dependent on GADD45B to induce NASH-fibrosis. FUS在TGFB1和COL1A1转录依赖GADD45B诱导nash纤维化中的新作用。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-17 DOI: 10.1093/jmcb/mjaf049

Chi Wu, Qiang Ding, Zhilin Zeng, Longjun Yang, Xiaozhen Song, Miaoxin Zhang, Panpan Lu, Rui Zhu, Zhipeng Du, Yixing Luo, Mei Liu

{"title":"Emerging role of FUS in TGFB1 and COL1A1 transcription dependent on GADD45B to induce NASH-fibrosis.","authors":"Chi Wu, Qiang Ding, Zhilin Zeng, Longjun Yang, Xiaozhen Song, Miaoxin Zhang, Panpan Lu, Rui Zhu, Zhipeng Du, Yixing Luo, Mei Liu","doi":"10.1093/jmcb/mjaf049","DOIUrl":"10.1093/jmcb/mjaf049","url":null,"abstract":"Fused in sarcoma (FUS), a DNA-RNA binding protein, affects gene transcription, while its role in non-alcoholic steatohepatitis (NASH)-fibrosis is not well understood. In this study, immunohistochemistry and western blot analysis were used to detect the expression of FUS in liver samples from patients with NASH and in LX-2 cells. Immunofluorescence staining showed that FUS co-localized with growth arrest and DNA damage 45β (GADD45B) in hepatic stellate cells (HSCs). Chromatin immunoprecipitation combined with quantitative PCR and luciferase reporter assays were performed to validate the binding sites and transcriptional activity of FUS to the TGFB1 and COL1A1 promoters. Gadd45b knockout (Gadd45b KO) and wild-type mice with the NASH-fibrosis model validated the role of GADD45B in NASH-fibrosis. Downregulation of GADD45B reduced HSC activation triggered by TGFB1 stimulation or FUS overexpression. Ameliorated collagen deposition and decreased nuclear FUS content in HSCs were detected in Gadd45b KO mice. Overall, this study suggests that FUS and GADD45B could be potential treatment targets for NASH-fibrosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Slirp2 modulates oogenesis via regulating mitochondrial protein translation. slrp2通过调节线粒体蛋白翻译调节卵子发生。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-17 DOI: 10.1093/jmcb/mjaf047

Jinguo Cao, Jiting Zhang, Zhaoqi Wu, Wei Luan, Yue Zhou, Huihui Huang, Lingling Li, Wen Hu

{"title":"Slirp2 modulates oogenesis via regulating mitochondrial protein translation.","authors":"Jinguo Cao, Jiting Zhang, Zhaoqi Wu, Wei Luan, Yue Zhou, Huihui Huang, Lingling Li, Wen Hu","doi":"10.1093/jmcb/mjaf047","DOIUrl":"10.1093/jmcb/mjaf047","url":null,"abstract":"Mitochondria are essential organelles responsible for generating adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). Despite having their own genome, mitochondria rely on a complex interplay with nuclear-encoded proteins to maintain their function, as mutations in these proteins can lead to mitochondrial dysfunction and associated diseases. Mutations in the SLIRP gene are known to cause severe human mitochondrial diseases, and loss of stem-loop interacting RNA-binding protein (SLIRP) function can impair mitochondrial mRNA stability and translation. However, in vivo roles of the SLIRP protein remain inadequately understood. Drosophila melanogaster serves as a powerful model for studying mitochondrial function, particularly in the context of reproductive system development and gametogenesis. In this study, we focus on the role of the fly Slirp2 in oogenesis. Loss of Slirp2 impairs mitochondrial protein synthesis, leading to reduced OXPHOS efficiency, diminished ATP production, and disrupted insulin/mTOR signaling. These defects ultimately promote reactive oxygen species-induced programmed cell death, resulting in infertility. Our findings provide novel insights into the mechanistic role of Slirp2 in mitochondrial function and reproductive biology in vivo. We demonstrate that Slirp2 exhibits species-specific regulation of mitochondrial translation, revealing its complex, context-dependent function. These results have broader implications for understanding mitochondrial diseases, suggesting that the effects of Slirp2 mutations may vary across different organisms and tissue types.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NOC4L coordinates neuronal and pharyngeal arch development by regulating ribosome biogenesis. no4l通过调节核糖体的生物发生来协调神经元和咽弓的发育。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-06-17 DOI: 10.1093/jmcb/mjaf052

Tujing Song, Yan Liu, Yunxiang Zhou, Xiaoyu Li, Liang Zhang, Guozhu Ning, Jingjing Zhang

{"title":"NOC4L coordinates neuronal and pharyngeal arch development by regulating ribosome biogenesis.","authors":"Tujing Song, Yan Liu, Yunxiang Zhou, Xiaoyu Li, Liang Zhang, Guozhu Ning, Jingjing Zhang","doi":"10.1093/jmcb/mjaf052","DOIUrl":"10.1093/jmcb/mjaf052","url":null,"abstract":"Mutations in ribosome biogenesis-related genes or functional defects in ribosomal proteins can lead to a class of autosomal genetic disorders characterized by tissue-specific defects, termed ribosomopathies. NOC4L, a critical factor in ribosome biogenesis, participates in the maturation of the 40S small ribosomal subunit. However, its functions in neural and cartilage development remain incompletely understood. In this study, through generation and phenotypic characterization of a zebrafish noc4l knockout model, we identified severe developmental abnormalities including microcephaly, micrognathia, and embryonic lethality. Further analyses revealed that noc4l loss-of-function results in reduced proliferation, differentiation blockade, and apoptotic activation. Mechanistically, sucrose gradient analysis demonstrated the disrupted ribosome biogenesis in noc4l mutants, with significantly reduced 40S/80S subunits and polysome levels, ultimately leading to overall translational inhibition and concurrent suppression of metabolic pathways. Pharmacological PPARγ activation via rosiglitazone partially rescued craniofacial malformations, ameliorated neurodevelopmental defects, and prolonged mutant life span. Although inhibition of the p53 pathway can partially rescue the phenotype, the p53 pathway and metabolic pathways are likely independent contributing factors. Our study reveals the molecular basis of developmental defects in noc4l mutants through impaired ribosome assembly and demonstrates the therapeutic potential of metabolic interventions for ribosomopathies.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A non-proteolytic role of SARS-CoV-2 PLpro in modulating host glycyl-tRNA synthetase activity. SARS-CoV-2 PLpro在调节宿主甘酰trna合成酶活性中的非蛋白水解作用

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-05-14 DOI: 10.1093/jmcb/mjag017

Jia-Li Lu, Yue Yin, Xiao-Long Zhou

引用次数: 0

ZBTB7B inhibits glioma tumorigenicity by upregulating GPR17 and CXCL10. ZBTB7B通过上调GPR17和CXCL10抑制胶质瘤的致瘤性。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-29 DOI: 10.1093/jmcb/mjaf043

Linmei Zhang, Haozhe Zhang, Chenxi Wang, Aoxin Jiang, Fei Zhao, Sifan Yang, Hong Lei, Xuelan Yu, Juan Ren, Chengfang Tang, Xiaofei Wang, Yanke Chen

{"title":"ZBTB7B inhibits glioma tumorigenicity by upregulating GPR17 and CXCL10.","authors":"Linmei Zhang, Haozhe Zhang, Chenxi Wang, Aoxin Jiang, Fei Zhao, Sifan Yang, Hong Lei, Xuelan Yu, Juan Ren, Chengfang Tang, Xiaofei Wang, Yanke Chen","doi":"10.1093/jmcb/mjaf043","DOIUrl":"10.1093/jmcb/mjaf043","url":null,"abstract":"The transcription factor ZBTB7B has been identified as a potential tumor suppressor through a CRISPR-Cas9-based functional screen of tumor-associated genes, as overexpression of ZBTB7B could significantly suppress tumor growth in the models of breast cancer brain metastasis, which prompted our further exploration of its inhibitory role in glioma. To elucidate the underlying mechanisms of this suppressive effect, lentiviral-mediated ZBTB7B overexpression was established in U118 and GL261 glioma cell lines, and systematic evaluation of tumorigenic capacity was performed through in vitro and xenograft assays. The results showed that ZBTB7B transcriptionally activated GPR17 expression, which suppressed protein kinase A phosphorylation, amplified mitochondrial reactive oxygen species generation, and triggered Caspase3-dependent apoptosis. Meanwhile, ZBTB7B upregulated CXCL10 secretion, which markedly enhanced CD4+ and CD8+ T cell accumulation. Clinical validation through multiplex immunofluorescence staining on a tissue microarray of 129 glioma samples revealed a progressive loss of ZBTB7B protein expression across WHO grades II to IV, inversely correlating with tumor malignancy. These findings demonstrate ZBTB7B as a dual-function tumor suppressor that concurrently induces intrinsic apoptosis and remodels the tumor immune microenvironment in glioma toward a 'hot' phenotype. Therefore, we propose ZBTB7B reactivation as a novel therapeutic strategy for glioma.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fam3C alters Golgi apparatus morphology and function in triple negative breast cancer. Fam3C改变三阴性乳腺癌的高尔基体形态和功能。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-29 DOI: 10.1093/jmcb/mjaf042

Annamarie C Dalton, Elisabeth R M Rochel, William S Streitfeld, Cécile Fréreux, Breege V Howley, Philip H Howe

{"title":"Fam3C alters Golgi apparatus morphology and function in triple negative breast cancer.","authors":"Annamarie C Dalton, Elisabeth R M Rochel, William S Streitfeld, Cécile Fréreux, Breege V Howley, Philip H Howe","doi":"10.1093/jmcb/mjaf042","DOIUrl":"10.1093/jmcb/mjaf042","url":null,"abstract":"Fam3C, also known as ILEI, is an established regulator of the epithelial-to-mesenchymal transition (EMT) and breast cancer stem cell phenotypes. Multiple cancer cell models and orthotopic animal model experiments have demonstrated a role for Fam3C in tumor progression and metastasis. Here, we establish Fam3C's impact on triple negative breast cancer (TNBC) patients and genetically engineered mouse models of spontaneous breast cancer tumor progression. Though Fam3C is a known secreted protein, we discovered its retention in the Golgi apparatus through anchoring of its signal peptide into the membrane before its signal peptide and pro-peptide are processed and removed. While retained in the Golgi apparatus, Fam3C affects the overall morphology of the organelle and its biological functions, including alterations in protein secretion and invasive potential. Expanding our knowledge of the biological mechanisms behind EMT will help develop therapies to specifically target cells with increased metastatic potential in TNBC.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications. 调节Notch信号通路和肿瘤血管生成的翻译后修饰：从分子机制到治疗应用。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-29 DOI: 10.1093/jmcb/mjaf051

Jiaan Wang, Meng Zhang, Donglai Wang

{"title":"Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.","authors":"Jiaan Wang, Meng Zhang, Donglai Wang","doi":"10.1093/jmcb/mjaf051","DOIUrl":"10.1093/jmcb/mjaf051","url":null,"abstract":"Tumorigenesis exhibits complex interactions with the vascular system. Targeting angiogenesis represents an emerging strategy for remodeling the tumor microenvironment. The Notch signaling pathway, a key regulatory mechanism, orchestrates tumor angiogenesis by modulating endothelial cell differentiation and vascular homeostasis. However, the clinical translation of Notch-targeted therapies is limited by severe toxicities due to lack of tissue specificity. Posttranslational modifications (PTMs) chemically regulate protein functions, thereby influencing multiple signaling cascades, including Notch signaling. Notably, Notch-associated PTMs are essential for signal transduction integrity. Some types of PTMs, such as glycosylation and ubiquitination, are the core for maintaining the integrity of the Notch signaling pathway. Dysfunctional Notch-related PTMs disrupt signal fidelity and drive pathological angiogenesis. This review systematically explores (i) crosstalk between Notch signaling and tumor angiogenesis, (ii) regulatory roles of PTMs on Notch molecules in tumor angiogenesis, and (iii) therapeutic potential of targeting Notch-related PTMs for anti-angiogenic strategies in tumor. We aim to elucidate the molecular nexus of PTMs-Notch-angiogenesis in tumor progression. Furthermore, we discuss therapeutic challenges in modulating Notch signaling pathway-dependent PTMs within tumor angiogenesis, focusing on critical barriers to their clinical translation in oncology.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0